Brief Report: The lincRNA Hotair Is Required for Epithelial-to-Mesenchymal Transition and Stemness Maintenance of Cancer Cell Lines
Brief Report: The lincRNA Hotair Is Required for Epithelial-to-Mesenchymal Transition and Stemness Maintenance of Cancer Cell Lines
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DOI：
10.1002/stem.1547
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发表时间：
2013-12-01
期刊：
影响因子：
5.2
通讯作者：
Silva, Wilson Araujo, Jr.
中科院分区：
文献类型：
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作者：
Alves, Cleidson Padua;Fonseca, Aline Simoneti;Silva, Wilson Araujo, Jr.
Hotair是最近描述的一类称为lincRNA（大基因间非编码RNA）的非编码RNA的一员。各种研究表明，Hotair通过招募染色质修饰复合物到特定的靶序列来调节表观遗传状态，最终导致几种基因的抑制。虽然Hotair在不同肿瘤类型中与转移和预后不良相关，但仍需深入表征其在癌症中的功能。在这里，我们研究了Hotair在上皮-间质转化（EMT）和癌症干细胞（CSCs）的产生和维持中的作用。我们发现用TGF-1治疗导致Hotair表达增加并触发EMT程序。有趣的是，通过siRNA消融Hotair表达可以阻止TGF-1刺激的EMT程序，也可以阻止结肠癌和乳腺癌细胞的集落形成能力。此外，我们观察到，与非干细胞亚群相比，结肠CSC亚群(CD133（+)/CD44(+)）表现出更高水平的Hotair。这些结果表明Hotair作为一个关键的调节因子，控制EMT中涉及的多种信号机制。总之，我们的数据表明Hotair在肿瘤发生中的作用是通过EMT触发和干性获得发生的。
Hotair is a member of the recently described class of noncoding RNAs called lincRNA (large intergenic noncoding RNA). Various studies suggest that Hotair acts regulating epigenetic states by recruiting chromatin-modifying complexes to specific target sequences that ultimately leads to suppression of several genes. Although Hotair has been associated with metastasis and poor prognosis in different tumor types, a deep characterization of its functions in cancer is still needed. Here, we investigated the role of Hotair in the scenario of epithelial-to-mesenchymal transition (EMT) and in the arising and maintenance of cancer stem cells (CSCs). We found that treatment with TGF-1 resulted in increased Hotair expression and triggered the EMT program. Interestingly, ablation of Hotair expression by siRNA prevented the EMT program stimulated by TGF-1, and also the colony-forming capacity of colon and breast cancer cells. Furthermore, we observed that the colon CSC subpopulation (CD133(+)/CD44(+)) presents much higher levels of Hotair when compared with the non-stem cell subpopulation. These results indicate that Hotair acts as a key regulator that controls the multiple signaling mechanisms involved in EMT. Altogether, our data suggest that the role of Hotair in tumorigenesis occurs through EMT triggering and stemness acquisition.